Development of a Visible Light Triggerable Traceless Staudinger Ligation Reagent

Abstract

A series of substituted 9-methylenylanthracene photocages for diphenylphosphinothioesters have been synthesized to explore their photo-uncaging properties by visible light. Substituents such as phenyl, p-trifluoromethylphenyl, p-methoxyphenyl, ethyn-1-ylbenzene, and 3,3-dimethylbut-1-yn-1-yl have been introduced in order to extend the π-conjugation of the photocage and to shift the wavelength response of the uncaging process to the visible spectral range. Among these new photocages, the (10-(3,3-dimethylbut-1-yn-1-yl)­anthracen-9-yl)­methyl has been shown to have the best performance in terms of fast photo-uncaging and minimal byproduct formation. It is responsive to both UV and visible photoexcitation. Quantum yields of the photoinduced heterolytic anthracenylmethyl–phosphorus bond cleavage at 366 and 416 nm were found to be 0.08 and 0.025, respectively. This photocage enables traceless Staudinger ligation to be triggered by photoirradiation in the visible spectral range for bioconjugation applications. We demonstrate this with a series of visible-light-induced oligopeptide syntheses via the conjugation of amino acid/oligopeptide building blocks by the characteristic peptide linkage attained by traceless Staudinger ligation. Yields of the resultant conjugated oligopeptides ranged from 31 to 43%. This new photocage opens up the possibility of in situ synthesis of functional proteins/peptides mediated by visible-light-induced photoclick processes for the regulation of cellular/metabolic functions of life systems.

Post‐Assembly Photomasking of Potassium Acyltrifluoroborates (KATs) for Two‐Photon 3D Patterning of PEG‐Hydrogels

“…This photocaging approach has been much rarer for other bioconjugation reactions such as tetrazine Diels-Alder or Staudinger reaction due to the lack of suitable photocaging methods. [23,24] Other alternative strategies to 3D photopatterning include enzymatic ligation of small peptide ligands [25][26][27] and photocatalyzed thiol-ene [28][29][30][31][32] or CuAAC [33] reactions. The latter two approaches do not necessarily require photocages, but utilize additional photocatalysts, which could result in undesired side reactions.…”

“…Several groups have developed systems combining photoreactions with fast bioconjugation reactions [11–17] in hydrogels using photocaged hydroxylamines, [18] thiols [19–21] or cyclooctynes [22] that undergo deprotection and bioconjugation upon irradiation. This photocaging approach has been much rarer for other bioconjugation reactions such as tetrazine Diels–Alder or Staudinger reaction due to the lack of suitable photocaging methods [23,24] . Other alternative strategies to 3D photopatterning include enzymatic ligation of small peptide ligands [25–27] and photocatalyzed thiol‐ene [28–32] or CuAAC [33] reactions.…”

Expansion of Phosphane Treasure Box for Staudinger Peptide Ligation

“…Finally, hydrolysis of amidophosphonium salt affords a stable amide bond between two peptide fragments. Further, Raine, Marx, Mamat, and Lam groups have expanded the scope of SPL using different phosphinols and phosphinothiols to prepare peptides, ranging in yields from very low to high (Scheme i–iv) . Notably, most of these strategies worked predominantly at Gly junction.…”

Photochemistry of a 9‐Dithianyl‐Pyronin Derivative: A Cornucopia of Reaction Intermediates Lead to Common Photoproducts

“…Later, several meso ‐methyl‐BODIPY‐based PPGs (Scheme b) have been designed to release LGs, representing synthetically accessible and thermally stable scaffolds with structurally easily adjustable optical and photophysical properties. Many other transition‐metal‐free PPG systems have been reported to date …”